95635-55-5 Usage
Description
Ranolazine, also known as N-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]acetamide (Ranexa), is an antianginal medication that was approved by the Food and Drug Administration (FDA) in January 2006 for the treatment of chronic angina. It is an active piperazine derivative that was patented in 1986 and is available in oral and intravenous forms. Ranolazine is evidenced with anti-ischemic/antianginal properties in patients with chronic angina without clinically significant changes in heart rate or blood pressure. It is a white solid and is marketed under the brand name Ranexa (Sensus).
Uses
Used in Cardiovascular Medicine:
Ranolazine is used as an antianginal medication for the treatment of chronic angina, a common symptom of coronary artery disease. It helps to alleviate chronic chest pain by altering the transcellular late sodium current, which in turn affects the sodium-dependent calcium channels during myocardial ischemia. This mechanism indirectly prevents the calcium overload associated with cardiac ischemia.
Ranolazine is also used as an anti-ischemic agent, providing potential benefits in cardiovascular conditions such as heart failure, acute and chronic myocardial ischemia, certain types of cardiac sodium channel gene mutations, and ventricular and supraventricular arrhythmias.
Used in Chronic Stable Angina (CSA) Treatment:
In patients with CSA, Ranolazine is used as an extended-release drug to treat chronic angina in those who have not responded to prior angina therapy. It helps to correct the imbalance between myocardial oxygen demand and supply, typically without producing significant reductions in heart rate or blood pressure.
References
[1] Bernard R. Chaitman, Ranolazine for the Treatment of Chronic Angina and Potential Use in Other Cardiovascular Conditions, New Drugs and Technologies, 2006, vol. 113, 2462-2472
[2] Bernard R. Chaitman, Sandra L. Skettino, John O. Parker, Peter Hanley, Jaroslav Meluzin, Jerzy Kuch and Carl J. Pepine, Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina, Journal of the American College of Cardiology, 2004, vol. 43, 1375-1382
Clinical Use
Add on therapy for angina
Synthesis
Two syntheses,
one from the inventors at Roche and other from a group in Hungary, of Ranolazine have been described in the
patent literature. The original synthesis is highlighted in the
Scheme. Reaction of 2,6-dimethylaniline 46 with chloroacetyl
chloride (47) in the presence of triethylamine for 4h at
0oC gave amide 48 in 82% yield. This chloro amide 48 was
reacted with piperazine in refluxing ethanol for 2 h to give
piperazinyl amide 50. Reaction of amide 50 with epoxide
intermediate 53, prepared by reacting 2-methoxy phenol 51
with epichlorohydrin, in refluxing isopropanol for 3 h followed
by treatment with HCl/methanol gave ranolazine dihydrochloride
(VII) in 73% yield.
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: avoid with disopyramide.
Antibacterials: concentration possibly increased
by clarithromycin and telithromycin - avoid
concomitant use; concentration reduced by
rifampicin - avoid.
Antifungals: concentration increased by ketoconazole
and possibly itraconazole, posaconazole and
voriconazole - avoid.
Antivirals: concentration possibly increased by
atazanavir, darunavir, fosamprenavir, indinavir,
lopinavir, ritonavir, saquinavir and tipranavir - avoid.
Beta-blockers: avoid with sotalol.
Ciclosporin: concentration of both drugs possibly
increased.
Grapefruit juice: concentration of ranolazine possibly
increased - avoid.
Statins: concentration of simvastatin increased -
maximum dose of simvastatin is 20 mg.
Tacrolimus: concentration of tacrolimus increased.
Metabolism
Extensively metabolised in the gastrointestinal tract and
liver. Four main metabolites have been identified.
Approximately 75% of a dose is excreted in the urine with
the remainder in the faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 95635-55-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,5,6,3 and 5 respectively; the second part has 2 digits, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 95635-55:
(7*9)+(6*5)+(5*6)+(4*3)+(3*5)+(2*5)+(1*5)=165
165 % 10 = 5
So 95635-55-5 is a valid CAS Registry Number.
InChI:InChI=1/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)
95635-55-5Relevant articles and documents
A preparation method of Ranolazine
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Paragraph 0038; 0041; 0045; 0046; 0049; 0050; 0053, (2019/03/28)
The present invention relates to the technical field of ranolazine, in particular to a ranolazine preparation method, the method comprises the following steps: piperazine through the hydroformylation reaction to obtain the 1 - formyl piperazine, then with 2 - chloro - N - (2, 6 - dimethyl-phenyl) acetamide for carrying out the alkylation reaction to obtain N - (2, 6 - dimethyl-phenyl) - 2 - (4 - formyl piperazine) acetamide, then through hydrolytic reaction to obtain N - (2, 6 - dimethyl-phenyl) - 2 - (1 - piperazinyl) acetamide, finally with 2 - (2 - methyl-phenoxymethyl) oxirane ring opening reaction to obtain the ranolazine. The invention preparation of the ranolazine purity is good, high yield.
In silico approach towards lipase mediated chemoenzymatic synthesis of (S)-ranolazine, as an anti-anginal drug
Sawant, Ganesh,Ghosh, Saptarshi,Banesh, Sooram,Bhaumik, Jayeeta,Chand Banerjee, Uttam
, p. 49150 - 49157 (2016/06/09)
An in silico modelling based biocatalytic approach for the synthesis of drugs and drug intermediates in enantiopure forms is a rationalized methodology over the organo-chemical routes. In this study, enzyme-ligand based docking was carried out using (RS)-ranolazine, as the model drug for the screening of a suitable biocatalyst for the kinetic resolution of the racemic drug. The differential interaction of the two enantiomers with the lipase was analyzed on the basis of docking score and H-bond interaction with the amino acid residues, which helped to define the trans-esterification mechanism. Ranolazine [N-(2,6-dimethylphenyl)-2-[4-(2-hydroxy)-3-(2-methoxyphenoxy)propylpiperazin-1-yl]acetamide], an anti-anginal drug, significantly reduces the frequency of anginal attack and has also been used for the treatment of ventricular arrhythmias, and bradycardia. Various lipases were examined via computational as well as wet lab screening and Candida antartica lipase in the form of CLEA was the most efficient one for the (S)-selective kinetic resolution of (RS)-ranolazine, with highest conversion and enantiomeric excess. This is the first report of the chemo-enzymatic synthesis of (S)-ranolazine where the whole drug molecule was used for lipase catalysis. The present study showed that the combination of in silico studies and a classical wet lab approach could change the paradigm of biocatalysis.
Process for the Preparation of Ranolazine
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, (2013/04/13)
A process for the preparation of ranolazine comprises the step of condensing N-(2,6-dimethylphenyl)-1-piperazinyl acetamide with a compound of formula (I) to obtain ranolazine, in which X is chlorine or bromine Ranolazine is prepared by condensing ring-opening halide which replaces epoxide in this process.